Medical implant

ABSTRACT

A endoprosthesis includes a body comprising a plurality of interconnected struts. The body includes a bioerodible metal. At least a first strut of the plurality of interconnected struts includes a stripe on the surface of the first strut. The stripe including a nitride of the bioerodible metal, a fluoride of the bioerodible metal, or a combination thereof. The stripe runs along the length of the first strut. The stripe is part of a continuous network of stripes on struts adjacent to the first strut.

TECHNICAL FIELD

This invention relates to medical implants, and more particularly toendoprostheses.

BACKGROUND

The body includes various passageways such as arteries, other bloodvessels, and other body lumens. These passageways sometimes becomeoccluded or weakened. For example, the passageways can be occluded by atumor, restricted by plaque, or weakened by an aneurysm. When thisoccurs, the passageway can be reopened or reinforced, or even replaced,with an endoprosthesis. An endoprosthesis is typically a tubular memberthat is placed in a lumen in the body. Examples of endoprosthesesinclude stents, covered stents, stent-grafts, and vascular closure pins.

Endoprostheses can be delivered inside the body by a catheter thatsupports the endoprosthesis in a compacted or reduced-size form as theendoprosthesis is transported to a desired site. Upon reaching the site,the endoprosthesis is expanded, for example, so that it can contact thewalls of the lumen.

The expansion mechanism can include forcing the endoprosthesis to expandradially. For example, the expansion mechanism can include the cathetercarrying a balloon, which carries a balloon-expandable endoprosthesis.The balloon can be inflated to deform and to fix the expandedendoprosthesis at a predetermined position in contact with the lumenwall. The balloon can then be deflated, and the catheter withdrawn.

In another delivery technique, the endoprosthesis is formed of anelastic material that can be reversibly compacted and expanded, e.g.,elastically or through a material phase transition. During introductioninto the body, the endoprosthesis is restrained in a compactedcondition. Upon reaching the desired implantation site, the restraint isremoved, for example, by retracting a restraining device such as anouter sheath, enabling the endoprosthesis to self-expand by its owninternal elastic restoring force.

Some endoprostheses are designed to erode under physiological conditionsso that most of the material of the endoprosthesis is naturally removedfrom the implantation site after a specific period of time.

SUMMARY

An endoprosthesis is described that includes a body including aplurality of interconnected struts and a stripe on the surface of afirst strut of the plurality of interconnected struts. The bodyincluding a bioerodible metal and the stripe including a nitride of thebioerodible metal, a fluoride of the bioerodible metal, or a combinationthereof. The stripe running along the length of the first strut. Thestripe being part of a continuous network of stripes on struts adjacentto the first strut.

The bioerodible metal can include iron or an alloy thereof and/ormagnesium or an alloy thereof. In some embodiments, the bioerodiblemetal of the body can have nano-crystal grains and a plurality ofcorrosion barrier layers in or between the nano-crystal grains. Thecorrosion barrier layers can include a metal nitride, a metal fluoride,or a combination thereof.

The stripe can have a maximum width of 250 micrometers and a minimumthickness of 100 nanometers. In some embodiments, the first strutincludes no more than one stripe. In some embodiments, the body isadapted for expansion from an initial diameter to an expanded diameterand includes a plurality of deformation points due to the expansion andat least one deformation point includes a plurality of stripes. Theplurality of stripes can be a part of the continuous network. In someembodiments, the stripe can includes a gradient from a surface adjacentto the bioerodible metal of the first strut having first percentage ofnitride, fluoride, or combination thereof to an outer surface having asecond percentage of nitride, fluoride, or combination thereof greaterthan the first percentage.

The first strut can also include a corrosion delaying layer surroundingthe first strut. The corrosion delaying layer can have a smallerthickness than a thickness of the stripe. The corrosion delaying layercan include a metal nitride, a metal fluoride, or a combination thereof.

The endoprosthesis, in some embodiments, can be a stent.

In another aspect, a medical implant is described that includes a bodythat includes a metal having nano-crystal grains and a plurality ofcorrosion barrier layers in or between the nano-crystal grains. Thecorrosion barrier layers can include a metal nitride, a metal fluoride,or a combination thereof. In some embodiments, the metal can bebioerodible. In some embodiments, the medical implant can include ametal nitride of the metal. In some embodiments, the medical implant canbe an endoprosthesis (e.g., a stent).

In another aspect, a method of forming an endoprosthesis is describedthat includes using a pulsed laser to transform a surface portion of abody comprising a bioerodible metal into a nitride of the bioerodiblemetal, a fluoride of the bioerodible metal, or a combination thereof.The body includes a plurality of interconnected struts. The body ispositioned within a nitrogen and/or fluorine environment during theapplication of the pulsed laser. In some embodiments, the surfaceportion of the body transformed into a nitride of the bioerodible metal,a fluoride of the bioerodible metal, or a combination thereof forms acontinuous network extending along a plurality of the interconnectedstruts. In some embodiments, the continuous network includes at leastone stripe has a maximum width of 250 micrometers and a minimumthickness of 100 nanometers. In some embodiments, the pulsed-laser is ananosecond pulsed laser. In some embodiments, the method furtherincludes forming the body by sintering a plurality of nanocrystallinebioerodible metal particles to produce the body including a metal bodyhaving nano-crystal grains and a plurality of corrosion barrier layersin or between the nano-crystal grains. The plurality of metal particlesincluding metal particles comprising a metal nitride, a metal fluoride,or a combination thereof, which form the corrosion barrier layers. Insome embodiments, endoprosthesis is a stent.

The details of one or more embodiments are set forth in the accompanyingdrawings and the description below. Other features, objects, andadvantages will be apparent from the description and drawings, and fromthe claims.

DESCRIPTION OF DRAWINGS

FIG. 1 is a perspective view of an embodiment of an expanded stent.

FIG. 2A is a perspective view of an embodiment of a stent strut.

FIG. 2B is a cross-sectional view of the stent strut of FIG. 2A.

FIG. 2C is a perspective view of the stent strut of FIG. 2A after thepartial erosion of the stent strut.

FIG. 2D is a perspective view of an embodiment of a stent strut.

FIGS. 3A and 3B depict a process of producing a nitrided stripe.

FIG. 4A is a perspective view of an embodiment of a stent strut.

FIG. 4B is a cross-sectional view of the stent strut of FIG. 4A.

FIGS. 5A-5C depict different stages of a method for producing a stenthaving corrosion barrier layers.

Like reference symbols in the various drawings indicate like elements.

DETAILED DESCRIPTION

Referring to FIG. 1, a stent 20 can have the form of a tubular memberdefined by a plurality of struts. The struts can include a plurality ofbands 22 and a plurality of connectors 24 that extend between andconnect adjacent bands. During use, bands 22 can be expanded from aninitial, small diameter to a larger diameter to contact stent 20 againsta wall of a vessel, thereby maintaining the patency of the vessel.Connectors 24 can provide stent 20 with flexibility and conformabilitythat allow the stent to adapt to the contours of the vessel.

The stent includes a bioerodible metal. Examples of bioerodible metalsinclude iron, magnesium, tungsten, zinc, and alloys thereof. Forexample, the bioerodible metal can be a bioerodible iron alloy thatincludes up to twenty percent by weight manganese, up to 10 percent byweight silver, and up to five percent by weight carbon. The bioerodiblemetal can also be a bioerodible magnesium alloy that includes up to ninepercent aluminum, up to five percent rare earth metals, up to fivepercent zirconium, up to five percent lithium, up to five percentmanganese, up to ten percent silver, up to five percent chromium, up tofive percent silicon, up to six percent yttrium, up to ten percent zinc.Suitable magnesium bioerodible alloys include ZK31, which includes threepercent zinc and one percent zirconium, ZK61, which includes six percentzinc and one percent zirconium, AZ31, which includes three percentaluminum and one percent zinc, AZ91, which includes nine percentaluminum and one percent zinc, WE43, which includes four percent yttriumand three percent rare earth metals, and WE54, which includes fivepercent yttrium and four percent rare earth metals. A stent including abioerodible metal can reinforce a reopened body passageway, yetbreakdown over time so that the stent is no longer present in the bodypassageway after a healing process is complete and the passageway nolonger needs reinforcement. Different bioerodible metals and stent strutstructures can have different erosion rates when exposed to aphysiological environment. Accordingly, the stent can be designed basedon the erosion characteristics of the stent struts to maintain thedesired structural properties for a desired period of time.

The stent also includes a nitride of the bioerodible metal, a fluorideof the bioerodible metal, or a combination thereof. Nitrides ofbioerodible metal include iron nitride, Fe₂N; magnesium nitride, Mg₃N₂;zinc nitride, Zn₃N₂; and tungsten nitride, WN₂. A nitride of abioerodible metal can have a higher erosion resistance than thebioerodible metal when the stent is implanted within a physiologicalenvironment. The inclusion of nitrides can also alter the hardness, wearresistance, corrosion resistance, and/or yield strength of thebioerodible metal.

As shown in FIGS. 2A-2D, a stent strut (e.g., a band 22 and/or aconnector 24) includes a body 26 including a bioerodible metal and astripe 28 including a nitride of the bioerodible metal, a fluoride ofthe bioerodible metal, or a combination thereof. For example, the body26 can include iron or an alloy thereof and the stripe 28 can includeiron nitride, Fe₂N. The body 26 forms the plurality of interconnectedstruts of the tubular member. The stripe 28 runs along the length of thestrut 22 or 24. The stripe 28 is part of a continuous network of stripesof the nitride of the bioerodible metal on adjacent struts.

The continuous network of stripes of nitride and/or fluoride of thebioerodible metal allows for areas surrounding the stripe 28 to erodewhen implanted within a physiological environment at a faster rate thanthe stripe 28. The presence of the continuous network of stripes canallow for a connection between different portions of the stent as thebody 26 erodes within a physiological environment, for example as shownin FIG. 2C. This connection reduces the instance and size of portions ofthe bioerodible body separating from the remainder of the stent andmigrating downstream of the implantation site.

The stripe can have a width of between 5 micrometers and the entirewidth of the strut, whereby the width of the stripe can be altered alongthe stripe by adjusting the optical system. Although FIG. 2A shows thestripe to be in the middle of the strut, it will be clear that thestripe can be positioned along the entire circumference of the strut. Insome embodiments, the stripe can have a width of between 10 micrometersand 30 micrometers (e.g., about 20 micrometers). An Excimer laser, asdiscussed below, can be focused down to a 5 micrometer spot size, whichcan allow for nitrided and/or fluorided stripes as thin as five to tenmicrometers. A stent strut can have a width of between 250 and 50micrometers. The size of the stripe 28 to the diameter of the stentstrut 22 or 24 can result in a minimal reduction in the erosion rate ofthe bioerodible metal body 26, yet can provide a network connectingdifferent portions of different struts even as the body erodes within aphysiological environment. As shown in FIGS. 2A-2C, some embodimentsincludes stent struts 22 or 24 having a single nitrided stripe 28.

Areas of the stent having higher stress levels can have additional metalnitrides and/or metal fluorides than the surrounding areas of the stentin some embodiments. For example, the bends in the bands 22 canexperience additional stress due the expansion of the stent. Thesedeformation points can therefore experience a faster rate of erosion.The additional metal nitrides and/or metal fluorides can reduce theinitial mass needed in high stress areas and can maintain the desiredmechanical performance after an initial amount of erosion. As shown inFIG. 2D, a bend in a band 22 can include multiple stripes 29 of anitrides and/or a fluorides of the bioerodible metal encasing the bend.The multiple stripes 29 can remain connected to the continuous networkof the nitrides and/or fluorides of the bioerodible metal.

The stripe 28 can include a gradient of nitride and/or fluoride from asurface adjacent to the bioerodible metal body 26 to an outer surface,with the outer surface having a higher percentage of nitrides and/orfluorides.

The stripe 28 can be formed on the surface of the body by transformingthe bioerodible metal of a precursor of the body into a nitride and/orfluoride of the continuous network. For example, pulsed-laser nitridingis one method of forming a nitrided stripe 28 on the surface of body 26.FIGS. 3A and 3B depict an example of a pulsed-laser nitriding process.For example, a stent 20 can be placed within a nitriding chamber 32containing nitrogen. In some embodiments, the nitriding chamber 32 canbe substantially free of oxygen and/or carbon dioxide. Portions of thestent body 26 are then subject to pulses of a laser at varyingwavelengths and pulse times. For example, body 26 can be subject tonanosecond Excimer laser pulses (55 ns), Nd-doped yttrium aluminumgarnet (Nd:YAG) laser pulses (8 ns), and/or ultra short Ti-sapphirelaser pulses (150 fs). As shown in FIG. 3A, an XeCl Excimer laser 34 canbe directed to and focused on a portion of a stent body 26 to produce anitrided stripe 28. A Fly Eye Homogenizer 36 and/or other opticalelement can be used to direct and focus the laser pulses onto aparticular location of the stent body 26. Additionally, a movable table38 can be used to move the stent body 26 during the nitriding process.As shown in FIG. 3B, the laser can create a plasma at the focus pointand can create a molten metal 27 along the surface of the stent body 26.The process can result in a gradient of nitride within the stripe havinga higher concentration of nitride along the outer surface of theresulting stent. The pulse time and power of the laser can impact thethickness of the nitrided stripe 28. The advantage of a pulsed lasersuch as an excimer laser is that the surface can repeatedly be moltenduring a very short timeframe in the order of the pulse time of thelaser, whereby the excited nitrogen gas can diffuse and react with themolten layer. The diffusion distance is a function of the pulse duringwhich the surface material is molten. The concentration of the nitridedlayer is determined as such by the number of pulses and the nitrogenconcentration in the surrounding atmosphere, whereas the depth of thenitrided layer is depending on the energy density in the pulse and thenumber of pulses. A nitrided surface of 1 micrometer can be achievedusing for example a 700 mJ pulse energy/square mm irradiation. Besidesusing a nitrogen atmosphere to achieve a nitriding effect, the use offluorine gas can within a chamber can achieve a fluoridizing effect. Asshown in FIG. 3B, the stripe can have a thickness of about 1 micrometer.

Stent 20 can also include a corrosion delaying layer 42 of a nitrideand/or fluoride of the bioerodible metal surrounding the exposedsurfaces of the stent body 26. The corrosion delaying layer 42 can havean approximately constant thickness. The thickness of the corrosiondelaying layer 42 is between 0.1 and 5 nanometers. For example, as shownin FIGS. 4A and 4B, the stent strut body 26 can include corrosiondelaying layer 42 around the circumference of the stent strut. The stentalso includes a nitrided and/or fluorided stripe 28, which remains afterthe corrosion delaying layer 42 erodes away and the stent body 26 erodesto help keep the plurality of stent struts connected. The corrosiondelaying layer 42 has a smaller thickness than stripe 28. For example,the corrosion delaying layer 42 can be produced by nitriding the entiresurface of a stent strut with a pulsed femtosecond laser, which cancreate a nitrided layer having a thickness of about 1 nanometer inthickness, while the continuous network of a nitrided stripe can beproduced with pulsed nanosecond laser, such as the Excimer laserdiscussed above, to produce a stripe having a thickness of about 1micrometer. For example, a description of a laser nitriding process isdescribed in Laser Nitriding of Metals, Influences of the AmbientPressure and the Pulse Duration, Meng Han, Gottingen 2001, which ishereby incorporated by reference.

The stent can have a body including a metal having nano-crystal grainsand a plurality of corrosion barrier layers in or between thenano-crystal grains. The corrosion barrier layers can include a metalnitride, a metal fluoride, or a combination thereof.

A stent body having metal nitride and/or metal fluoride corrosionbarrier layers in or between the nano-crystal grains can be produced bya powder sintering and nitriding/fluoridizing process. For example, apowder of a metal can be produced by mechanical milling (MM). Forexample, a ball mill can be used at room temperature in an argon gas orother atmosphere to produce a metal powder. The mechanically milled ormechanically alloyed powders are easily reduced down to a crystal graindiameter of about 10 to 20 nm by mechanical energy applied by ballmilling. Examples of mechanical milling processes are described in U.S.Patent Application No. 2006/0127266, which is hereby incorporated byreference.

The metal powder can be a bioerodible metal, such as those describedabove. In some embodiments, the metal powder includes only a singlemetal, such as iron, without the presence of alloying elements. In otherembodiments, the metal powder can be an alloy.

The metal powder can be partially nitrided and/or fluorided before asintering process. The partial nitriding and/or fluoridizing of themetal powder prior to the sintering process can result in a stent bodyhaving increased mechanical strength and internal corrosion barriers.For example, FIG. 5A depicts a nanocrystalline iron powder put into alayer in a flat pan. The flat pan can then be placed within a nitridingchamber and portions of powder can be nitrided. FIG. 5B depicts ananocrystalline iron powder in the flat pan partially treated with lasernitriding. Additionally, metal powder could be separated into twogroups, with only one group being nitrided. The groups could then bemixed and/or layered prior to sintering. Additionally, the ratios of thenitrided to non-nitrided metal powders can be varied for differentportions of a resulting stent.

The partially nitrided metal powder can then be sintered to create metalhaving metal nitride and/or fluoride corrosion barrier layers in orbetween the nano-crystal grains. For example, the metal powder can bevacuum charged into a stainless steel tube (sheath) forforming-by-sintering by means of sheath rolling using a rolling machineat a temperature that is about 10% lower than the melting temperature ofthe metal powder. Examples of sintering processes are described in U.S.Patent Application No. 2006/0127266, which is hereby incorporated byreference.

The sintered metal can then be shaped into a medical device, such asstent 20. FIG. 5C depicts a stent strut 22 or 24 including the sinteredmetal structure that includes a bulk structure that resembles a marblecake. For example, the sintered metal can then be shaped into a stent byforming a tube out of the sintered metal and cutting the tube to formbands 22 and connectors 24 to produce an unfinished stent. Areas of theunfinished stent affected by the cutting can be subsequently removed.The unfinished stent can be finished to form stent 20. Finishing caninclude, for example, polishing or other surface treatments and/orapplication of drug-eluting coatings. In some embodiments, finishing thestent can further include producing a network of nitrided and/orfluorided stripes and/or to producing a corrosion delaying layer 42, asdiscussed above. In other embodiments, the sintered metal can be shapedinto other medical devices such as orthopedic implants; bioscaffolding;bone screws; aneurism coils, and other endoprostheses such as coveredstents and stent-grafts.

Stent 20 can be of any desired shape and size (e.g., superficial femoralartery stents, coronary stents, aortic stents, peripheral vascularstents, gastrointestinal stents, urology stents, and neurology stents).Depending on the application, the stent can have a diameter of between,for example, 1 mm to 46 mm. In certain embodiments, a coronary stent canhave an expanded diameter of from 2 mm to 6 mm. In some embodiments, aperipheral stent can have an expanded diameter of from 5 mm to 24 mm. Incertain embodiments, a gastrointestinal and/or urology stent can have anexpanded diameter of from 6 mm to about 30 mm. In some embodiments, aneurology stent can have an expanded diameter of from about 1 mm toabout 12 mm. An Abdominal Aortic Aneurysm (AAA) stent and a ThoracicAortic Aneurysm (TAA) stent can have a diameter from about 20 mm toabout 46 mm.

The stent 20 can, in some embodiments, be adapted to release one or moretherapeutic agents. The term “therapeutic agent” includes one or more“therapeutic agents” or “drugs.” The terms “therapeutic agents” and“drugs” are used interchangeably and include pharmaceutically activecompounds, nucleic acids with and without carrier vectors such aslipids, compacting agents (such as histones), viruses (such asadenovirus, adeno-associated virus, retrovirus, lentivirus and a-virus),polymers, antibiotics, hyaluronic acid, gene therapies, proteins, cells,stem cells and the like, or combinations thereof, with or withouttargeting sequences. The delivery mediated is formulated as needed tomaintain cell function and viability. A common example of a therapeuticagent includes Paclitaxel.

The stent 20 can, in some embodiments, also include one or more coatingsoverlying the surface portion 32. In some embodiments, a surface coatingcan further delay the erosion of the surface portion 32. In someembodiments, a coating can be a drug-eluting coating that includes atherapeutic agent.

Stent 20 can be used, e.g., delivered and expanded, using a catheterdelivery system. Catheter systems are described in, for example, WangU.S. Pat. No. 5,195,969, Hamlin U.S. Pat. No. 5,270,086, andRaeder-Devens, U.S. Pat. No. 6,726,712. Stents and stent delivery arealso exemplified by the Sentinol® system, available from BostonScientific Scimed, Maple Grove, Minn.

In some embodiments, stents can also be a part of a covered stent or astent-graft. In other embodiments, a stent can include and/or beattached to a biocompatible, non-porous or semi-porous polymer matrixmade of polytetrafluoroethylene (PTFE), expanded PTFE, polyethylene,urethane, or polypropylene.

In some embodiments, stents can be formed by fabricating a wire having anitrided stripe 28, nitride corrosion barrier layers, and/or a corrosiondelaying layer 42 and knitting and/or weaving the wire into a tubularmember.

All publications, references, applications, and patents referred toherein are incorporated by reference in their entirety.

Other embodiments are within the claims.

1. A endoprosthesis comprising: a body comprising a plurality ofinterconnected struts, the body comprising a bioerodible metal, and atleast a first strut of the plurality of interconnected struts includinga stripe on the surface of the first strut, the stripe comprising anitride of the bioerodible metal, a fluoride of the bioerodible metal,or a combination thereof, the stripe running along the length of thefirst strut, the stripe being part of a continuous network of stripes onstruts adjacent to the first strut.
 2. The endoprosthesis of claim 1,wherein the bioerodible metal comprises iron or an alloy thereof.
 3. Theendoprosthesis of claim 1, wherein the bioerodible metal comprisesmagnesium or an alloy thereof.
 4. The endoprosthesis of claim 1, whereinthe stripe has a maximum width of 250 micrometers and a minimumthickness of 100 nanometers.
 5. The endoprosthesis of claim 1, whereinthe first strut comprises no more than one stripe.
 6. The endoprosthesisof claim 1, wherein the body is adapted for expansion from an initialdiameter to an expanded diameter and comprises a plurality ofdeformation points due to the expansion, wherein at least onedeformation point includes a plurality of stripes, the plurality ofstripes being part of the continuous network.
 7. The endoprosthesis ofclaim 1, wherein the stripe includes a gradient from a surface adjacentto the bioerodible metal of the first strut having first percentage ofnitride, fluoride, or combination thereof to an outer surface having asecond percentage of nitride, fluoride, or combination thereof greaterthan the first percentage.
 8. The endoprosthesis of claim 1, wherein thefirst strut further comprises a corrosion delaying layer surrounding thefirst strut, the corrosion delaying layer having a smaller thicknessthan a thickness of the stripe, the corrosion delaying layer comprisinga metal nitride, a metal fluoride, or a combination thereof.
 9. Theendoprosthesis of claim 1, wherein the bioerodible metal of the body hasnano-crystal grains and a plurality of corrosion barrier layers in orbetween the nano-crystal grains, the corrosion barrier layers comprisinga metal nitride, a metal fluoride, or a combination thereof.
 10. Amedical implant comprising a body that includes a metal comprisingnano-crystal grains and a plurality of corrosion barrier layers in orbetween the nano-crystal grains, the corrosion barrier layers comprisinga metal nitride, a metal fluoride, or a combination thereof.
 11. Themedical implant of claim 10, wherein the metal is bioerodible.
 12. Themedical implant of claim 10, wherein the medical implant comprises ametal nitride of the metal.
 13. The medical implant of claim 10, whereinthe medical implant is an endoprosthesis.
 14. The medical implant ofclaim 10, wherein the medical implant is stent.
 15. A method of formingan endoprosthesis comprising: using a pulsed laser to transform asurface portion of a body comprising a bioerodible metal into a nitrideof the bioerodible metal, a fluoride of the bioerodible metal, or acombination thereof, the body including a plurality of interconnectedstruts, the body being positioned within a nitrogen and/or fluorineenvironment during the application of the pulsed laser.
 16. The methodof claim 15, wherein the surface portion of the body transformed into anitride of the bioerodible metal, a fluoride of the bioerodible metal,or a combination thereof forms a continuous network extending along aplurality of the interconnected struts.
 17. The method of claim 16,wherein the continuous network includes at least one stripe has amaximum width of 250 micrometers and a minimum thickness of 100nanometers.
 18. The method of claim 15, wherein the pulsed-laser is ananosecond pulsed laser.
 19. The method of claim 15, further comprisingforming the body by sintering a plurality of nanocrystalline bioerodiblemetal particles to produce the body including a metal body havingnano-crystal grains and a plurality of corrosion barrier layers in orbetween the nano-crystal grains, the plurality of metal particlescomprising metal particles comprising a metal nitride, a metal fluoride,or a combination thereof, which form the corrosion barrier layers. 20.The method of claim 15, wherein the endoprosthesis is a stent.